Rapamycin attenuates PLA2R activation-mediated podocyte apoptosis via the PI3K/AKT/mTOR pathway

This study aimed to investigate the crosstalk between PLA2R activation and mTOR signaling in a human podocyte cell line. We demonstrated that podocyte apoptosis was induced by Group IB secretory phospholipase A2 (sPLA2IB) in a concentration- and time-dependent manner via upregulation of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and mTOR, and inhibited by rapamycin or LY294002. Furthermore, aberrant activation of the PI3K/AKT/mTOR pathway triggers both extrinsic (caspase-8 and caspase-3) and intrinsic (Bcl-2-associated X protein [BAX], B-cell lymphoma 2 [BCL-2], cytochrome c, caspase-9, and caspase-3) apoptotic cascades in podocytes. The therapeutic implications of our findings are that strategies to reduce PLA2R activation and PI3K/AKT/mTOR pathway inhibition in PLA2R-activated podocytes help protect podocytes from apoptosis. The therapeutic potential of rapamycin shown in this study provides cellular evidence supporting the repurposing of rapamycin for MN treatment.PMID:34700229 | DOI:10.1016/j.biopha.2021.112349
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Source Type: research